THE PROTECTIVE EFFECTS OF L-ARGININE AFTER LIVER ISCHAEMIA REPERFUSION INJURY IN A PIG MODEL/

Hepatic ischaemia/reperfusion is characterized by circulatory and meta bolic derangement, liver dysfunction, and tissue damage, To evaluate t he role of L-arginine, a substrate of nitric oxide, in ischaemia/reper fusion injury, total liver ischaemia was induced for 120 min in 22 Lan drace x Large White female pigs, which were randomly assigned to a tre atment group (12 animals) or a control group (12 animals), An L-argini ne bolus (540 mg/kg i.v.) was administered to the treatment group 1 h before clamping the hepatic hilum, at clamping, at reperfusion, and at 1 and 2 h after reperfusion, The control animals received normal sali ne and an i.v. infusion, Liver function tests and analysis of serum, e rythrocyte, and tissue malondialdehyde contents were performed at comm encement of laparotomy, before reperfusion, and at 30 min and 7 days a fter reperfusion, Liver biopsies were taken at laparotomy, at 30 min, and at 7 days after reperfusion for histological and ultrastructural e xamination, Assessment of apoptosis included in situ end-labelling ana lysis and DNA gel electrophoresis, Survival at 7 days was better in th e treated animals than in the controls (9/10 vs, 7/12), Tissue malondi aldehyde content, aspartate aminotransferase, and lactate dehydrogenas e levels were lower in the treatment group, in which morphological cha nges were significantly less evident than in the controls 30 min after reperfusion. At 7 days, differences between the groups with respect t o cell integrity were apparent only on ultrastructural analysis, Glyco gen content, 7 days after reperfusion, was higher in the treatment gro up than in the controls: 70.25 per cent vs, 21.66 per cent positive he patocytes (score 3 vs. score 1), Multiparametric analysis showed fewer apoptotic cells in the treatment group at all times. Our data show th at the administration of L-arginine reduces damage to liver tissue aft er ischaemia/reperfusion injury in a pig model. This may be explained not only by the known vasodilator, anti-aggregation, and superoxide in activation effects of increased nitric oxide release, but possibly als o by some other action of L-arginine, such as its influence on cellula r metabolism, (C) 1997 John Wiley & Sons, Ltd.